JP6574191B2 - Capryloylalanine ethyl ester as a penetration enhancer - Google Patents

Description

1. FIELD OF THE INVENTION The present invention relates to the use of caprolol-alanine ethyl ester as a penetration enhancer in cosmetic or other topical compositions, as well as the active (effective) ) Ingredients, specifically UV filters, anti-acne active agents, anti-aging active agents, anti-inflammatory agents, hair conditioners, antiperspirants or deodorants, whitening agents, self-tanning agents, and vitamins The present invention relates to a cosmetic composition comprising a combination with a beneficial substance for skin such as a kind.

2. Description of Prior Art Prior to the start of use in cosmetic compositions, the first field of application of transdermal absorption enhancers, also called penetration enhancers, was pharmaceutical transdermal therapeutic systems. Delivery of pharmaceutically active agents through the skin is very interesting because it allows for systemic drug delivery avoiding the hepatic first pass mechanism. However, the passage of most molecules through the skin is hampered by skin barrier properties. The penetration enhancer can be used to promote absorption of the target substance. Various chemical groups have been studied for their penetration promoting activity and numerous modes of action and interaction sites have been identified. Among the mechanisms of action are 1) adapting the solvent properties to the substance of interest and improving partitioning into the skin, 2) interacting with the intercellular lipid matrix, thereby changing the barrier structure, There is a penetration promotion effect by 3) denaturing intercellular proteins to increase permeability and / or 4) providing a storage effect in the skin.

  One of the first skin penetration enhancers described and used in pharmaceutical compositions was dimethyl sulfoxide (DMSO), a universal solvent belonging to sulfoxide.

  The first substance specifically aimed at being a skin penetration enhancer was azone laurocapran, an extremely lipophilic substance that improves penetration by interacting with lipids in the stratum corneum.

  Pyrrolidones such as N-methyl-2-pyrrolidone (NMP) have also been used to promote percutaneous absorption of anti-inflammatory drugs, but there are toxicological concerns that cannot be used.

  Although the use of terpenes such as menthol has been described, its odor can make it difficult to use. Menthol not only increases the solubility of osmotic drugs by creating eutectic systems with these active agents, but also increases permeability by altering the barrier properties of the stratum corneum by interacting with its lipid domains. Fatty acids, mainly unsaturated fatty acids (oleic acid), have been successfully used as accelerators. Alcohols such as ethanol or lauryl alcohol dissolve and extract lipids in the stratum corneum and interact with the lipid bilayer, whereas fatty acids are highly lipophilic, thereby modifying the lipid domain of the stratum corneum, thereby , Mainly improve the permeability of hydrophilic molecules.

  In recent years, more active ingredients have been used in cosmetics. Because of the topical route of application, penetration enhancers have also been found in the means for personal care applications. The main focus of applying penetration enhancers to the cosmetic field is not systemic delivery of the substance, but to increase the penetration of the active agent into the skin and improve the efficacy of the cosmetic. Common penetration enhancers, such as solvent systems that act by increasing drug distribution, such as propylene glycol, or agents that promote hydration of the stratum corneum, are used in cosmetic compositions.

  In general, cosmetics need to have good skin compatibility, and the ingredients should have a good toxicity profile.

  Various studies have shown that amino acid esters are effective penetration enhancers with low toxicity and very good biocompatibility.

In EP 0 552 505 A1, which is a European patent application, the formula R ¹ NH—R ³ —COOR ² wherein R ¹ is a hydrogen atom, an acyl group having 1 to 20 carbon atoms, or 1 to 20 R ² is a hydrogen atom or a hydrocarbon group having 1 to 20 carbon atoms, R ³ is —CHR ⁴ — or benzyl, and R ⁴ is A transdermal absorption enhancer of a pharmacologically active substance is disclosed, including an amino acid derivative having a hydrogen atom, a methyl group, an isopropyl group, a 2-methylpropyl group, or a 1-methylpropyl group. The most effective candidate for the absorption enhancer proposed for a pharmacologically active substance selected from the group consisting of indomethacin, ketoprofen, prednisolone and pindolol was Nn-dodecanoylglycine ester. Dodecanoyl-amino acids such as alanine, valine, leucine, and ethyl esters of isoleucine were also tested.

  N-lauroyl-isopropyl sarcosinate was the subject of various patent applications in the cosmetic field:

  N-lauroyl-isopropyl sarcosinate has many components and activities of the lipid phase in polymer-thickened cosmetic and dermatological compositions as outlined in the international patent family of WO 2003/039448 It is a candidate substance selected to dissolve the agent. The described polymers have an average molecular weight of less than 100,000 DA, preferably in the range of 1000 to 30000, a) a polymer backbone with hydrocarbon repeating units containing at least heteroatoms, and b) optionally at least one pendant A fatty chain and / or at least one terminal fatty chain, optionally functionalized, having from 12 to 120 carbon atoms, bonded to the unit, the fatty chain comprising a heteroatom unit and a fatty chain Including said fatty chain, corresponding to 40-98% of the total. These compositions can also include UV filters.

  The subject of European patent application EP 1277462 A1 is a cosmetic or dermatological composition intended for artificial skin tanning, comprising at least one self-tanning agent and at least one N-acylamino acid ester. there were. The addition of N-acyl amino acid esters has been shown to improve the coloring and stability of self-tanning agents in compositions for artificial skin tanning. Isopropyl N-lauroyl sarcosinate was selected for use with self-tanning agents.

  In European patent application EP 1 269 980 A1, a composition comprising at least one 1,3,5-triazine derivative and at least one N-acyl amino acid ester, and to protect the skin, lips or skin from UV radiation The use thereof in or for the manufacture of a cosmetic composition is disclosed. The N-acyl amino acid ester selected for combination with the 1,3,5-triazine derivative was isopropyl N-lauroyl sarcosinate, which improved the sun protection factor of the composition.

  The invention of US 2005/0065251 A1, which is a US application, is a cosmetic composition structured with polyamide, characterized in that it comprises at least one organic UV filter and at least one amino acid N-acylated ester. It relates to its use in or for preparing a composition for protecting the skin, lips or skin appendages. A preferred amino acid N-acetylated ester was also isopropyl N-lauroyl sarcosinate.

  The use of isopropyl N-lauroyl sarcosinate has some limitations. Isopropyl N-lauroyl sarcosinate is a semi-solid compound with a waxy texture and its melting point is higher than room temperature, making it difficult to incorporate into a dermatological composition. This melting point also prevents the substance from melting on the skin.

EP 0 552 505 A1 WO 2003/039448 EP 1277462 A1 EP 1 269 980 A1 US 2005/0065251 A1

  The object of the present invention is to provide an effective penetration enhancer for topical compositions with good tolerability and improved compatibility with other cosmetic additives, which is a cosmetic composition. Can be easily incorporated into. Penetration enhancers can also provide good sensory profiles.

3. DESCRIPTION OF THE INVENTION The present invention relates to the use of caprolol-alanine ethyl ester as a penetration enhancer in cosmetic compositions and other topical or oral compositions. In the present invention, permeation can also include permeation and absorption.

  One embodiment of the present invention relates to a cosmetic composition comprising capryloylalanine ethyl ester as a penetration enhancer. These compositions comprise a caprylol-alanine ester in combination with an active agent, preferably a UV filter, an anti-acne active agent, an anti-aging active agent, an anti-inflammatory agent, a hair conditioning agent, an antiperspirant or a deodorant. , Whitening agents, self-tanning agents, and vitamins in combination.

  Surprisingly, it has been found that a composition comprising caprylol-alanine ethyl ester gives the skin a moisturizing feel without an unpleasant stickiness, while at the same time providing a very good sensory profile. Caprylol-alanine ethyl ester also promotes skin penetration of the active agent, particularly hydrophilic active agent, over other N-acyl amino acid esters.

  The cosmetic composition can comprise 0.1-90% by weight of capryloylalanine ethyl ester, based on the total composition, generally 1-30% by weight, preferably 2%, based on the total composition. It will contain ~ 10 wt%, more preferably 2-5 wt%.

  The Hansen Solubility Parameter (HSP) distance to the stratum corneum of capryloylalanine ethyl ester was found to be smaller than well-known established reference examples such as ethyldiethylene glycol and DMI, which show sufficient potential as skin penetration enhancers. The Hansen solubility parameter is an important indicator of good partitioning into the stratum corneum when the molecule is liquid at RT and has a sufficiently small molar volume.

  The addition of caprolol-alanine ethyl ester as a penetration enhancer provides many advantages for cosmetic compositions containing active agents. The skin compatibility of a formulation comprising an active agent with adverse compatibility properties, in particular, achieves the intended effect faster and / or targets the desired tissue (layer) more efficiently and / or. This can be improved because lower concentrations of the active ingredient can be used.

  The penetration enhancer itself is less likely to penetrate through the skin than DMI and is therefore unlikely to be available systemically. Furthermore, capryloyl-alanine ethyl ester can be metabolized in the skin, thus contributing to an improved toxicity profile.

  In addition, capryloyl-alanine ethyl ester has been found to have a moisturizing effect similar to other emollients and is found to be absorbed faster than other emollients, so its application in topical compositions is Bring about a pleasant sensory profile.

  Caprolol-alanine ethyl ester is an odorless liquid material and is therefore very easily incorporated into cosmetic and topical compositions. The resulting formulation has a very good physicochemical stability. As a polar emollient, caprolol-alanine ethyl ester has beneficial solubilizing properties and can improve the dispersion and distribution of the active agent on the tissue.

Active compound The preparation according to the invention comprises caprolol-alanine ester in combination with a cosmetically acceptable active compound.

  According to the invention, the active compound (one or more compounds) is advantageously effective in UV filters, anti-acne active agents, anti-aging active agents, anti-inflammatory agents, hair growth regulators, hair or hair follicles. Drugs, antiperspirants or deodorants, whitening agents, self-tanning agents, peptides, oligopeptides, proteins, acetylsalicylic acid, atropine, azulene, hydrocortisone and derivatives thereof such as hydrocortisone-17-valerate, vitamins, In particular, vitamin B and D systems, specifically vitamin B1, vitamin B12, vitamin D, vitamin A and their derivatives, such as retinyl palmitate, vitamin E or their derivatives, such as tocopheryl acetate And derivatives thereof such as ascorbyl glucoside, niacinamide, panthenol, bisaboro Le polydocanol, unsaturated fatty acids such as essential fatty acids (usually called vitamin F), specifically γ-linolenic acid, oleic acid, eicosapentaenoic acid, docosahexaenoic acid, and derivatives thereof, chloramphenicol, Caffeine, prostaglandin, thymol, camphor, squalene, plant and animal extracts or other products such as evening primrose oil, borage oil or carob bean oil, fish oil, Cod-liver oil, plus ceramide and ceramide-like compounds, fragrance extract, green tea extract, water lily extract, liquorice extract, and witch hazel, anti-dandruff activity Compounds (e.g. selenium disulfide, zinc pyrithione, piroctone, olamine, clambazole, octopirox, polidoca And active compound complexes, such as γ-oryzanol, and active compound complexes of calcium salts such as calcium pantothenate, calcium chloride, and calcium acetate. .

  Specifically, when the composition according to the present invention is used for the treatment and prevention of symptoms of intrinsic and / or extrinsic skin aging and for the treatment and prevention of the harmful effects of ultraviolet radiation on the skin and hair, One or more active compounds can also be selected from the group consisting of NO synthase inhibitors. A preferred NO synthase inhibitor is nitroarginine.

  The one or more active compounds are furthermore advantageously catechol and bile acid esters of catechol, and aqueous or organic extracts derived from plants or parts of plants containing catechol or bile acid esters of catechol, for example , Selected from the group including leaves of Theaceae plant family, specifically, leaves of Camellia sinensis (green tea). Catechols are a group of compounds interpreted as hydrogenated flavones or anthocyanidins, and catechols include derivatives of catechol (catechol, 3,3 ′, 4 ′, 5,7-flavanpentaol, 2- ( 3,4-dihydroxyphenyl) -chroman-3,5,7-triol). Epicatechol ((2R, 3R) -3,3 ′, 4 ′, 5,7-flavanpentaol) is also an active compound advantageous in the present invention.

  Furthermore, preferred active compounds include (-)-catechol, (+)-catechol, (-)-catechol gallate, (-)-gallocatechol gallate, (+)-epicatechol, (-)-epicatechol There are polyphenols or catechols from the group consisting of: (-)-epicatechol gallate, (-)-epigallocatechol, and (-)-epigallocatechol gallate.

  Flavon and derivatives thereof (often referred to generically as “flavones”) are also active compounds advantageous in the present invention. Further advantageous active compounds include celicoside, pyridoxol, vitamin K, biotin and fragrances.

  Preferably, the active compound (one or more compounds) is very advantageously a hydrophilic active compound, an α-hydroxy acid such as lactic acid or salicylic acid or a salt thereof such as Na lactate, Ca lactate, Or it can be selected from the group consisting of urea, allantoin, serine, sorbitol, glycerol, milk protein, panthenol, or chitosan, such as lactic acid TEA.

  Most preferably, the active compound is a UV filter, an anti-acne active agent, an anti-aging active agent, an anti-inflammatory agent, a hair growth regulator, an agent having an effect on the hair or hair follicle, an antiperspirant or deodorant, a whitening agent , Self-tanning agents, and vitamins.

a) UV filter It has been studied that the selected penetration enhancer significantly improves the solubilization of the UV filter, thereby greatly improving the UV protection properties of the cosmetic composition of the present invention.

  Caprolol-alanine ethyl ester has interesting UV filter solubilizing properties. It is possible to increase the solubility of known UV filters such as ethylhexyltriazone (Uvinul T150) over other commonly used solvents, e.g. 23% by weight versus 16% by weight in dibutyl adipate. It is therefore possible to increase the concentration in the solvent. This can subsequently be an advantage of designing a formulation with an improved sensory profile. A more homogeneous distribution and better penetration into the upper stratum corneum can also be achieved.

  Furthermore, the UV protection effect of the UV filter which is a pigment and acts physically is also improved by adding caprylol-alanine ethyl ester. Due to the good diffusion properties of the accelerator, this type of UV filter improves the homogeneity of the distribution in cosmetic compositions and also on the skin after application (application).

  Accordingly, the active compound (one or more compounds) can be very particularly advantageously selected from the group consisting of optical filter active compounds.

  Suitable light filter active compounds include substances that absorb ultraviolet (UV) radiation in the UV-B and / or UV-A region. According to these, it is understood that the organic substance can absorb ultraviolet rays and can release the absorbed energy again in the form of longer wavelength radiation such as heat. The organic material can be oil-soluble or water-soluble. A suitable UV filter is, for example, 2,4,6-triaryl-1,3,5-triazine, in which the aryl group in each case is hydroxyl, alkoxy, in particular methoxy, as well as alkoxycarbonyl, In particular, it can have at least one substituent, preferably selected from methoxycarbonyl and ethoxycarbonyl. More suitable are p-aminobenzoic acid esters, cinnamic acid esters, benzophenones, camphor derivatives, and pigments that prevent UV radiation, such as titanium dioxide, talc, and zinc oxide. Titanium dioxide pigments are particularly preferred.

Examples of oil-soluble UV-B filters that can be used include the following materials:
3-benzylidene camphor and derivatives thereof, such as 3- (4-methylbenzylidene) camphor; 4-aminobenzoic acid derivatives, preferably 4- (dimethylamino) -benzoic acid 2-ethylhexyl ester, 4- (dimethylamino) ) Benzoic acid 2-octyl ester and 4- (dimethylamino) benzoic acid amyl ester; cinnamic acid ester, preferably 4-methoxycinnamic acid 2-ethylhexyl ester, 4-methoxycinnamic acid propyl ester, 4-methoxy cinnamic acid Isoamyl ester, 4-methoxycinnamic acid isopentyl ester, and 2-cyano-3-phenyl-cinnamic acid 2-ethylhexyl ester (octocrylene); salicylic acid ester, preferably salicylic acid 2-ethylhexyl ester, salicylic acid 4-isopropylbenzyl ester, And salicylic acid homomenthyl ester; benzophenone derivatives, preferred Preferably, 2-hydroxy-4-methoxybenzophenone, 2-hydroxy-4-methoxy-4′-methylbenzophenone, and 2,2′-dihydroxy-4-methoxybenzophenone; benzalmalonic acid ester, preferably 4-methoxy Benzalmalonic acid di-2-ethylhexyl ester; triazine derivatives such as 2,4,6-trianilino- (p-carbo-2'-ethyl-1'-hexyloxy) -1,3,5-triazine (octyl) Triazone), and dioctylbutamide triazone; propane-1,3-dione, such as 1- (4-tert-butylphenyl) -3- (4′-methoxyphenyl) propane-1,3-dione .

Possible water-soluble substances include
2-phenylbenzimidazole-5-sulfonic acid and its alkali metal, alkaline earth metal, ammonium, alkylammonium, alkanolammonium, and glucammonium salts;
A benzophenone sulfonic acid derivative, preferably 2-hydroxy-4-methoxybenzophenone-5-sulfonic acid and its salts;
3-benzylidene camphor sulfonic acid derivatives, such as 4- (2-oxo-3-bornylidenemethyl) benzenesulfonic acid and 2-methyl-5- (2-oxo-3-bornylidene) sulfonic acid, and their There is salt.

  Particular preference is given to the use of cinnamic acid esters, preferably 4-methoxycinnamic acid 2-ethylhexyl ester, 4-methoxycinnamic acid isopentyl ester, and 2-cyano-3-phenyl-cinnamic acid 2-ethylhexyl ester (octocrylene).

  Use of benzophenone derivatives, specifically 2-hydroxy-4-methoxybenzophenone, 2-hydroxy-4-methoxy-4'-methylbenzophenone, and 2,2'-dihydroxy-4-methoxybenzophenone, and propane-1 , 3-diones, such as 1- (4-tert-butylphenyl) -3- (4′-methoxyphenyl) propane-1,3-dione, are more preferred.

Possible normal UV-A filters include:
Benzoylmethane derivatives such as 1- (4'-tert-butylphenyl) -3- (4'-methoxyphenyl) -propane-1,3-dione, 4-tert-butyl-4'-methoxydibenzoylmethane, Or 1-phenyl-3- (4′-isopropylphenyl) -propane-1,3-dione and the like;
-Amino-hydroxy-substituted derivatives of benzophenone, such as N, N-diethylamino-hydroxybenzoyl-n-hexyl-benzoate.

  The UV-A and UV-B filters can of course also be used in a mixture.

  Further suitable UV filter substances are listed in the table below:

  In addition to the above two groups of primary sunscreen substances, use an antioxidant type of second sunscreen that blocks the photochemical cellular reaction chain that occurs when UV rays penetrate the skin. You can also. Typical examples are UV-induced functional and / or structural changes in superoxide dismutase, catalase, tocopherol (vitamin E), and ascorbic acid (vitamin C).

  A further group of suitable active agents are anti-inflammatory substances that have a beneficial effect on skin damage caused by UV light. Examples of such materials include, but are not limited to, bisabolol, phytol, and phytantriol, and acetylsalicylic acid.

  The list of active compounds and active compound combinations mentioned above that can be used in the compositions according to the invention is, of course, not intended to be limiting. The active compounds can be used alone or in any desired combination with each other.

  The amount of such active compound (one or more compounds) in the composition according to the invention is preferably 0.001 to 30% by weight, particularly preferably 0.05 to 20% by weight, based on the total weight of the composition. %, Specifically 1 to 10% by weight.

b) Self-tanning agents and whitening agents Caprolol-alanine ethyl ester improves the uniformity of self-tanning agents. With the addition of penetration enhancers, self-tanning and whitening agents can be applied much more uniformly, resulting in a homogeneous skin tanning effect or skin whitening effect.

  Suitable self-tanning agents include pyrazoline-4,5-dione derivatives, glutaraldehyde, alloxan, ninhydrin, 4,4-dihydroxypyrazoline-5-dione, and dihydroxyacetone. A preferred self-tanning agent for use with penetration enhancers is dihydroxyacetone (DHA). The amount of self-tanning agent is in the range of 0.05 to 10% by weight, preferably 0.1 to 5% by weight, based on the total weight of the cosmetic composition.

  Typically, whitening agents are required to penetrate the skin and diffuse its function, many of which are essential to prevent the formation of melanin and consequently act on the melanocytes of the skin including. Examples of whitening agents are arbutin, ferulic acid, kojic acid, coumaric acid, plant extracts, and ascorbic acid (vitamin C).

c) Anti-acne active agents Anti-acne active agents such as anti-inflammatory agents, antibiotics, retinoids, antibacterial agents, and keratolytic agents often cause undesirable side effects. Thus, it would be advantageous if the dose of these active agents could be reduced by improving penetration and distribution into the upper skin layers, sebaceous cells, and / or skin pores.

  Anti-acne actives used in combination with penetration enhancers include α-hydroxy acids (AHA) including glycolic acid and lactic acid; β-hydroxy acids such as salicylic acid; benzoyl peroxide; hydroxyquinoline; sulfur; antibiotics Topical retinoids derived from vitamin A including, for example, tetracycline, dapsone, doxycycline, minocycline, erythromycin, clindamycin, etc .; azelaic acid; retinoids; isotretinoin; tretinoin, isotretinoin, motretinide, adapalene, and tazarotene; nicotinamide; Allantoin; and selected from the group consisting of plant extracts.

d) Anti-aging actives Many keratolytic agents used as anti-acne actives are also known as anti-aging actives. In particular, there are α- and β-hydroxy acids, as well as retinoids and retinoic acids.

  Other types of anti-aging actives include vitamins, protein hydrolysates, peptides and modified peptides, β-glucans, and plant extracts.

e) Vitamins According to the present invention, vitamin B group vitamins, provitamins, or vitamin precursors that are preferably used, or derivatives thereof, and 2-furanone derivatives, in particular, are: Includes:
Vitamin B1, common name thiamine, chemical name 3-[(4'-amino-2'-methyl-5'-pyrimidinyl) methyl] -5- (2-hydroxyethyl) -4-methylthiazolium chloride,
Vitamin B2, common name riboflavin, chemical name 7,8-dimethyl-10- (1-D-ribityl) -benzo [g] pteridine-2,4 (3H, 10H) -dione. Riboflavin occurs, for example, in free form in whey, and other riboflavin derivatives can be isolated from bacteria and yeast. According to the present invention, also suitable riboflavin stereoisomers can be isolated from fish meal or fish liver, and include lysoflavin having a D-arabityl group instead of the D-ribityl group.
Vitamin B3. The compounds nicotinic acid and nicotinamide (niacinamide) are often mentioned by this name. According to the invention, nicotinamide is preferred.
Vitamin B5 (pantothenic acid and panthenol). It is preferred to use panthenol. Panthenol derivatives that can be used in accordance with the present invention include, in particular, esters and ethers of panthenol, and cationic derivatized panthenol. In a further preferred embodiment of the invention, 2-furanone derivatives can be used in addition to pantothenic acid or panthenol. Particularly preferred derivatives include dihydro-3-hydroxy-4,4-dimethyl-2 (3H) furanone, 4-hydroxymethyl-butyrolactone (Merck), which is also a commercially available substance, 4-hydroxymethyl-butyrolactone ( Merck), 3,3-dimethyl-2-hydroxy-butyrolactone (Aldrich), and 2,5-dihydro-5-methoxy-2-furanone (Merck), all stereoisomers are also explicitly included.
These compounds advantageously provide hydration and skin soothing properties to the skin cosmetics according to the invention.
Vitamin B6, which is not a certain substance, is understood to be a derivative of 5-hydroxymethyl-2-methylpyridin-3-ol, known by the trivial names pyridoxine, pyridoxamine, and pyridoxol.
Also referred to as vitamin B7 (biotin), vitamin H or “skin vitamin”. Biotin is (3aS, 4S, 6aR) -2-oxohexahydrothienol [3,4-d] imidazole-4-valeric acid.

  According to the present invention, panthenol, pantolactone, nicotinamide and biotin are particularly preferred as vitamins.

f) Hair conditioners Hair conditioners include:
-Hair growth stimulants that induce new hair cycle growth, increase growth rate or increase hair shaft diameter;
-Agents that have an effect on the hair, e.g. increasing the amount of hair, the gloss of the hair and the strength and thickness of the hair;
-Drugs that have an effect on hair follicles, and
-Hair growth inhibitor.

  In order to be an effective hair conditioner, it is usually necessary to penetrate percutaneously and through the hair follicle to the hair root. Therefore, when a penetration enhancer is added, the effect of the hair conditioner is directly enhanced.

  Most hair conditioning agents are hair growth stimulating actives that prevent and delay hair loss. Drug treatment with hair growth stimulating active agents is often associated with the use of drugs including but not limited to minoxidil, finasteride, dutasteride, bicalutamide, flutamide, progesterone derivatives, or pregnane derivatives.

  Other hair growth stimulants used in cosmetic compositions include zinc and zinc salts, unsaturated fatty acids, procyanidin oligomers, γ-linolenic acid, biotin, placental extract, pantothenic acid and their derivatives, prostaglandins, For example, bimatoprost, methylamido dihydro noralfaprostal, and / or tafluprost; magnesium, allantoin, theophylline, and barley, grape seeds, apple seeds, saw palmetto, Ubaurushi, green tea, propolis, sorghum There are plant extracts including but not limited to extracts from eleuthero root, pine bark.

  Purines and purine derivatives are known to reduce hair loss.

  For example, known scalp blood circulation promoters for the treatment of alopecia include acetylcholine derivatives, nicotinic acid derivatives, plant extracts derived from pepper, plant extracts derived from ginseng, swertia herb Including, but not limited to, plant extracts of origin.

  Suitable agents that have an effect on hair follicles include taurine and taurine derivatives, or L-carnitine or L-carnitine derivatives.

  Hair growth inhibitors are mainly used for cosmetic reasons. They are niacinamide, thiazolidinone derivatives, protein kinase C inhibitors, ornithine decarboxylase inhibitors, trihydroxypurine salts; soy protein hydrolysates, urea, sold as Pilinhib® (BASF Beauty Care Solutions) , Salicylic acid, willow extract, hamamelis extract, arnica extract, hypericum extract, salix alba extract, and combinations of menthol.

g) Deodorants or antiperspirants Cosmetic deodorants counteract, mask or remove body odors. Due to the effect of skin bacteria during apocrine sweating, a body odor is produced along with the formation of degradation products with an unpleasant odor. Thus, the deodorant contains active ingredients that act as antimicrobial agents, odor absorbers, and / or enzyme inhibitors.

  Suitable antimicrobial agents are basically all substances effective against gram positive bacteria, such as 4-hydroxybenzoic acid and its salts and esters, N- (4-chlorophenyl) -N ′ -(3,4-dichlorophenyl) urea, 2,4,4'-trichloro-2'-hydroxydiphenyl ether (triclosan), 4-chloro-3,5-dimethylphenol, 2,2'-methylenebis (6-bromo- 4-chlorophenol), 3-methyl-4- (1-methylethyl) phenol, 2-benzyl-4-chlorophenol, 3- (4-chlorophenoxy) -1,2-propanediol, 3-iodo-2 -Proponyl butyl carbamate, chlorhexidine, 3,4,4'-trichlorocarbanilide (TTC), antibacterial fragrance, thymol, thyme oil, eugenol, clove oil, menthol, mint oil, farnesol, phenoxy -Ethanol, glycerol monocaprate Glycerol monocaprylate, glycerol monolaurate (GML), diglycerol monocaprate (DMC), salicylic acid N-alkylamides such as N-octylsalicylamide or N-decylsalicylamide.

  Suitable enzyme inhibitors include, for example, esterase inhibitors. These inhibitors are preferably trialkyl citrates such as trimethyl citrate, tripropyl citrate, triisopropyl citrate, tributyl citrate, specifically triethyl citrate (Hydagen® CAT ) This substance inhibits enzyme activity, thereby reducing the generation of odor. Other substances that are suitable esterase inhibitors include dicarboxylic acids and esters thereof, such as sterol sulfate or phosphate sterols such as lanosterol, cholesterol, campesterol, stigmasterol, and sulfate or phosphate esters of sitosterol, For example, glutaric acid, monoethyl glutarate, diethyl glutarate, adipic acid, monoethyl adipate, diethyl adipate, malonic acid, and diethyl malonate, hydroxycarboxylic acids and esters thereof such as citric acid, malic acid, tartaric acid, Or diethyl tartrate and the like, as well as zinc glycinate.

  Appropriate odor absorbers are substances that can absorb and sufficiently retain odor generating compounds. They reduce the partial pressure of each component, thereby reducing the diffusion rate of each component. What is important in this process is that the fragrance must be kept so as not to be weakened. Odor absorbers are ineffective against bacteria. They are, for example, as a main component, zinc complexes of ricinoleic acid, or certain most odor neutralizing fragrances known to those skilled in the art as “retaining agents”, such as extracts of Radnam or styrax, or Including certain abietic acid derivatives and the like. Odor masking agents include fragrances or perfume oils, and in addition to their function as odor masking agents, each fragrance note is given to the deodorizer. What can be mentioned as perfume oils are, for example, mixtures of natural and synthetic fragrances. Natural fragrances include extracts from flowers, stems and leaves, fruits, pericarp, roots, trees, herbs and grasses, needles and branches, and resins and balsams. Also suitable are animal raw materials such as musk cats and castrium. Typical synthetic fragrance compounds include esters, ethers, aldehydes, ketones, alcohols, and hydrocarbon type products. Examples of ester-type aromatic compounds include benzyl acetate, p-tert-butylcyclohexyl acetate, linalyl acetate, phenylethyl acetate, linalyl benzoate, benzyl formate, allyl cyclohexylpropionate, styryl propionate, and benzyl salicylate. is there. Ethers include, for example, benzyl ethyl ether, and aldehydes include, for example, linear alkanals having 8 to 18 carbon atoms, citral, citronellal, citronellyloxy-acetaldehyde, cyclamenaldehyde, hydroxycitronellal, Including lyial and bolgeonal; ketones include, for example, ionone and methyl cedryl ketone; alcohols include anethole, citronellol, eugenol, isoeugenol, geraniol, linalool, phenylethyl alcohol, and terpineol; hydrocarbons The class mainly includes terpenes and balsams. However, it is preferred to use a mixture of different fragrances that together create a pleasant scent. Relatively low volatility essential oils, mainly used as aromatic components, are also suitable as perfume oils, e.g. sage oil, camomile oil, clove oil, melissa oil, mint oil, cinnamon leaf oil Linden blossom oil, juniper berry oil, vetiver oil, olibanum oil, galvanum oil, labdanum oil, and lavandin oil. Bergamot oil, dihydromyrsenol, lyral, rilal, citronellol, phenylethyl alcohol, hexylcinnamaldehyde, geraniol, benzylacetone, cyclamenaldehyde, linalool, boisambrene forte, ambroxan, indole, Hezion, sandelice, lemon oil, mandarin oil, orange oil, allyl amyl glycolate, cyclovertal, lavandine oil, ony salvia oil, damascon, geranium oil bourbon, cyclohexyl salicylate, iso-E -Iso-E-super, Fixolide NP, Evernil, iraldein gamma, phenylacetic acid, geranyl acetate, benzyl acetate, rose oxide, lomilat, irotyl, and It is preferred to use floramat alone or as a mixture.

Antiperspirants Antiperspirants reduce the production of sweat by acting on the activity of the eccrine sweat glands, thus countering underarm moisture and body odor. Aqueous or anhydrous formulations of antiperspirants usually contain an astringent active ingredient.

  As an astringent antiperspirant active ingredient, there are mainly aluminum salts, zirconium salts, or zinc salts. Such suitable antihydrotic active ingredients include, for example, aluminum chloride, aluminum chlorohydrate, aluminum dichlorohydrate, aluminum sesquichlorohydrate, and complex compounds thereof such as 1,2-propylene glycol. Complex compounds with, aluminum hydroxy allantoate, aluminum chloride tartrate, aluminum zirconium trichlorohydrate, aluminum zirconium tetrachlorohydrate, aluminum zirconium pentachlorohydrate, and their complex compounds, for example with amino acids such as glycine There are complex compounds.

Cosmetic composition and / or pharmaceutical composition The penetration enhancer according to the invention is used in cosmetic compositions or other topical compositions, preferably emulsion type compositions, most preferably capryloylalanine ethyl ester Used as a penetration enhancer in W / O type emulsion. These cosmetic compositions or other topical compositions comprise a penetration enhancer in combination with at least one component, which is different from the penetration enhancer and is a cosmetically active compound, emulsifier , Surfactants, preservatives, perfume oils, thickeners, hair polymers, hair and skin conditioners, graft polymers, water-soluble or dispersible silicone-containing polymers, gelling agents, care agents, coloring agents, coloring agents, dyes , Pigments, agents for imparting consistency, moisturizers, re-oiling agents, collagen, protein hydrolysates, lipids, antioxidants, antifoaming agents, antistatic agents, emollients, And softeners.

Antioxidants are advantageously amino acids (e.g. glycine, histidine, tyrosine, tryptophan) and their derivatives, imidazoles (e.g. urocanic acid) and their derivatives, peptides such as D, L-carnosine, D- Carnosine, L-carnosine and their derivatives (e.g. anserine), carotenoids, carotenes (e.g. β-carotene, lycopene), and their derivatives, chlorogenic acid and their derivatives, lipoic acid and their derivatives ( (E.g., dihydrolipoic acid), aurothioglucose, propyl-thiouracil, and other thiols (e.g., thioredoxin, glutathione, cysteine, cystine, cystamine, and their glycosyl esters, N-acetyl esters, methyl esters, ethyl esters, propyls) Esther, Amyles Butyl ester and lauryl ester, palmitoyl ester, oleyl ester, γ-linoleyl ester, cholesteryl ester, and glyceryl ester) and their salts, dilauryl thiodipropionate, distearyl thiodipropionate, thiodipropionic acid And their derivatives (esters, ethers, peptides, lipids, nucleotides, nucleosides, and salts), and very low tolerated doses (e.g., pmol to μmol / kg) of sulfoximine compounds (e.g., butionine sulfoximine, homocysteine) Sulfoxyimines, buthionine sulfones, penta-, hexa- and hepta-thionine sulfoximines), (metal) chelating agents (e.g. α-hydroxy-fatty acids, palmitic acid, phytic acid, lactoferrin), α-hydroxy Acids (e.g. Citric acid, lactic acid, malic acid), humic acid, bile acid, bile extract, bilirubin, biliverdin, EDTA and their derivatives, unsaturated fatty acids and their derivatives (e.g., γ-linolenic acid, linoleic acid, oleic acid) ), Folic acid and derivatives thereof, ubiquinone and ubiquinol and derivatives thereof, vitamin C and derivatives thereof (e.g. sodium ascorbate, ascorbyl palmitate, ascorbyl phosphate Mg, ascorbyl acetate), tocopherols and derivatives (e.g. vitamin acetate E, tocotrienol), vitamin A and derivatives (vitamin A palmitate), and benzoin resin coniferylbenzoate, rutinic acid and their derivatives, α-glycosylrutin, ferulic acid, furfurylidene, carnosine, butylhydroxytoluene, butylhydride Kishianisoru, nordihydrocapsaicin Guay acknowledgment resin acid, nordihydroguaiaretic acid, trihydroxy butyronitrile phenone, uric acid and derivatives thereof, mannose and derivatives thereof, zinc and derivatives thereof (e.g. ZnO, ZnSO _4), selenium and their Derivatives (eg selenium methionine) and stilbenes and their derivatives (eg stilbene oxide, trans-stilbene oxide) are selected.

Capryloylalanine ethyl ester production method Capryloylalanine ethyl ester (KE4610) is produced in a two-step process.

Process 1: Alanyl acylation with capryloyl chloride in aqueous solution by the Schotten-Baumann method.
120 kg (0.74 kmol) capryloyl chloride is added to a vigorously stirred aqueous solution of 66 kg (0.74 kmol) alanine in 100 kg water and 30 kg ethanol at 15 ° C. over 4-5 hours. The pH value is maintained between 11 and 12 by constantly adding 20% NaOH (about 140 kg). The pH value should not be less than 10.5 so that the temperature does not exceed 25 ° C. After completing the addition of capryloyl chloride, the reaction mixture is post-reacted at 20-25 ° C. and a pH of 9 or higher for about 2 hours.

  The mixture is heated to 70 ° C. with stirring for 1 hour, and then the pH is adjusted to 1.8-2.3 by adding about 80 kg of 30% aqueous HCl. After stopping the agitation, the system begins to separate into an aqueous salt solution and an organic layer containing 85-90% capryloylalanine, caprylic acid (hydrolysis product), ethanol, and a little water. The aqueous phase is removed and the organic layer (about 205 kg) is further processed in step 2.

Process 2: Esterification and purification The organic layer is esterified by removing water / ethanol by distillation and adding fresh ethanol until the desired degree of esterification (at least 80-90%) is reached. The esterification can be adjusted by GC analysis or by measuring the residual acid number. The esterification mixture is then fractionally distilled. The low boilers water, ethanol and caprylic acid are removed at temperatures up to 105 ° C. at less than 1 mbar and the final product can be distilled at 137-140 ° C. at less than 1 mbar. In order to obtain a high purity ester, the mixture is adjusted to pH = 7 by adding a certain amount of soda or NaOH before distillation, thereby converting the volatile acid into a non-distillable salt. Can do. Preferred products have an acid number of less than 1 after distillation.

  The efficacy of the penetration enhancer is independent of the manufacturing method, and therefore other methods of manufacturing capryloylalanine ethyl ester known to those skilled in the art are possible and suitable.

[4. Examples]
4.1 Penetration test by applying the accelerator directly to the skin (pre-incubation method)
The purpose of this study was to measure the efficacy of the following three test substances (one of the closest prior art penetration enhancers) that act as skin permeation enhancers in cosmetic formulations.
Dimethylisosorbide (DMI), well known as a penetration enhancer-used in cosmetics-Penetration enhancer 1 (PE1)-capryloylalanine ethyl ester-Penetration enhancer 2 (PE2)-the closest prior art molecule, Dodeci Roylalanine ethyl ester

The test was conducted at an independent testing organization specializing in permeability testing. Formulation 1 (W / O formulation) is a used formulation and does not contain a penetration enhancer. The skin is preincubated with selected penetration enhancers (DMI, PE1, and PE2), and after 30 minutes incubation, the formulation is removed from the skin surface and radiolabeled ³ H-caffeine or ³ H-acetic acid Formulation 1 mixed with vitamin E was applied.

  The effect of three penetration enhancers on the skin absorption rate of caffeine and vitamin E acetate (representative hydrophilic and lipophilic cosmetic active agents, respectively) incorporated in the w / o formulation was investigated. Radiolabeled caffeine and vitamin E acetate were used as markers. In vitro skin permeability tests were performed 3 times over 24 hours using dermatomized human skin (approximately 500 μm thick). Samples were taken from the acceptor compartment at four sampling times (1, 3, 6 and 24 hours) and screened for permeation enhancing effects.

Transdermal absorption of test compounds ³ H-caffeine and ³ H-vitamin E acetate was observed by measuring the amount of radiolabeled substance in the acceptor medium.

  Test compounds were quantified by liquid scintillation counting. Prior to in vitro permeation experiments, the linearity of both isotope scintillation measurements was verified.

Test Method Description Raw Material and Method

  According to the European Commission's SCCP guidelines, human skin resected from surgical procedures enters human skin under in vivo conditions and is suitable for in vitro testing to simulate the permeation and permeation processes of passing compounds. It is a system.

  In the penetrability test, human skin (female abdominal skin) of one donor skinned to a thickness of 500 ± 100 μm was used, and the test was performed three times. Full thickness skin was prepared from skin biopsy material and stored at -20 ° C.

  According to OECD guidelines, the permeability of skin is not changed when stored at -20 ° C for up to 466 days. The skin was used immediately after thawing. Repeated freeze-thaw cycles were avoided.

Formulation 1 (without penetration enhancer) was mixed with radiolabeled ³ H-caffeine (specific activity 60 Ci / mmol) and ³ H-vitamin E acetate (specific activity 50 Ci / mmol) as a control. Applied directly to the skin. Radiolabeled samples were prepared as follows. Formulation 1 was mixed with either radiolabeled ³ H-caffeine or ³ H-vitamin E acetate to result in 290000 cpm / 50 μl or 1264557 cpm / 50 μl, respectively. One of three different penetration enhancers (DMI, PE1, and PE2) was applied to the skin, followed by a W / O formulation mixed with radioactive material.

Krebs Ringer buffer (KRB, pH = 7.4) was prepared according to the internal standard operating procedure. KRB was used as the acceptor medium for ³ H-caffeine. ^{For 3} H-vitamin E acetate, KRB supplemented with 2% bovine serum albumin (BSA) was used as the acceptor medium. Using a solution of ³ H-caffeine and ³ H-vitamin E acetate, the detection method was verified and the linearity was evaluated.

Transport test The permeability test was performed by measuring 4 times on human skin using test and reference items. In the transport test, the cut skin was cut using a punch with a diameter of 24 mm, and the skin thickness of each sample was measured at 5 points. Subsequently, skin pieces were fixed on a cylindrical glass Franz cell used as a diffusion chamber. The volume of the lower (acceptor) chamber is about 12 ml, while the volume of the upper (donor) chamber is variable. The skin was inserted with the dermis layer facing down so that the stratum corneum of the skin was at the top.

  Before applying the formulation, penetration enhancers (20 μl each) were spread on the skin. This method was used to avoid the effects resulting from possible interactions between penetration enhancers and the components in the cosmetic composition.

PE2 (C12), which is a solid at room temperature, was gradually melted in a water bath (35-40 ° C.) and applied as a liquid. After a 30 minute incubation, the liquid penetration enhancer was gently removed using a cotton ball. For PE2 solidified on the skin, the solid film was removed by tweezers. Thereafter, 50 μl of the formulation was applied to the skin surface. The acceptor medium was adjusted to 32 ° C. with a thermostat and stirred continuously at a speed of 400 rpm. The skin diffusion area was about 1.8 cm ² . Permeability through the skin into the acceptor medium was observed over 24 hours. The acceptor medium was sampled by removing 200 μl samples at four different time points after 1, 3, 6 and 24 hours. After removing the sample volume, the acceptor medium was supplemented with pre-warmed KRB / KRB + 2% BSA. The active ingredient concentration in the acceptor chamber was corrected to account for dilution by sampling. The removed sample was mixed with 210 μl or 500 μl of scintillation cocktail at 200 rpm for at least 1 hour, and the radioactivity was measured by scintillation counting.

The results are shown as activity release [cpm cm ⁻² ] into the acceptor medium plotted against time. The amount of active ingredient in unknown samples was calculated by linear regression using the corresponding calibration.

Results The results of the permeability test are summarized in the table below.

  The highest permeation enhancing effect was detected with PE1. Transport from this formulation is about 5 times higher compared to controls without any penetration enhancer, substantially higher than DMI or PE2.

  With vitamin E acetate, a much slower transport could be detected. The reason may be due to insufficient release of this lipophilic substance from the formulation and / or to bind to the lipophilic structure within the skin. The applied penetration enhancers DMI and PE1 show only a slight penetration enhancing effect during the 24 hour detection time. However, PE2 reduces vitamin E acetate transport and, in effect, acts as a retarder. Compared with the prior art molecule PE2 (dodecylalanine ethyl ester), PE1 (capryloylalanine ethyl ester) enhanced the penetration effect by 1.5 times.

Conclusion
For the hydrophilic substance caffeine incorporated into the w / o formulation, the most effective permeation enhancer is PE1. DMI increased caffeine transport by a factor of about 2 and PE2 increased caffeine transport by a factor of about 3.

  Transport of lipophilic vitamin acetate acetate incorporated into the same w / o formulation is not significantly enhanced by the permeation enhancer used. Nevertheless, the use of capryloylalanine ethyl ester as a penetration enhancer does not show a delayed effect on the penetration of the lipophilic molecule, vitamin E acetate, compared to DMI or dodeciloylalanine ethyl ester. Still preferred.

4.2 Penetration test with accelerator incorporated in W / O formulation (incorporation method)
The described test was partially repeated in a similar experimental setup using the following three test substances to act as a skin permeation enhancer when incorporated into a cosmetic formulation and not applied directly to the skin .
・ Dimethylisosorbide (DMI), a well-known penetration enhancer-used in cosmetics ・ Penetration enhancer 1 (PE1)-capryloylalanine ethyl ester ・ Penetration enhancer 2 (DGME)-Transcutol (Gattefossee) ), Diethylene glycol monoethyl ether

Formulation 1 (W / O formulation) was a basic formulation and a reference formulation that did not contain any penetration enhancer. This time, the skin was not preincubated with the selected penetration enhancers (DMI, PE1, and DGME), but 5% penetration enhancers were each incorporated into Formulation 1 and the resulting formulation was radiolabeled. Again mixed with ³ H-caffeine or ³ H-vitamin E acetate.

result:
The results of the permeability test are summarized in Table 6.

CONCLUSION Even when a penetration enhancer is incorporated into the W / O formulation, PE1 is the most effective permeation enhancer for the hydrophilic marker compound caffeine. Compared to a reference formulation without any enhancer, DMI caused a slight decrease in caffeine transport and DGME slightly increased transport.
Some embodiments are shown below.
Item 1
A cosmetic composition comprising capryloylalanine ethyl ester as a penetration enhancer.
Item 2
Item 2. The cosmetic composition according to Item 1, comprising 0.1 to 90% by weight of capryloylalanine ethyl ester relative to the total composition.
Item 3
Item 3. The cosmetic composition according to Item 1 or 2, wherein the cosmetic composition is an emulsion composition.
Item 4
A cosmetic composition comprising capryloylalanine ethyl ester and at least one active agent.
Item 5
Active agents are UV filters, anti-acne active agents, anti-aging active agents, anti-inflammatory agents, hair growth regulators, agents that have an effect on hair or hair follicles, antiperspirants or deodorants, whitening agents, self-tanning agents , Peptides, oligopeptides, proteins, acetylsalicylic acid, atropine, azulene, hydrocortisone and their derivatives such as hydrocortisone-17-valerate, vitamins, in particular vitamin B and D systems, specifically vitamin B1, Vitamin B12, Vitamin D, Vitamin A and their derivatives such as retinyl palmitate, Vitamin E or their derivatives such as tocopheryl acetate, Vitamin C and their derivatives such as ascorbyl glucoside, niacinamide, panthenol Bisabolol polidocanol, unsaturated fatty acid, eg essential Fatty acids (usually called vitamin F), such as γ-linolenic acid, oleic acid, eicosapentaenoic acid, docosahexaenoic acid, and their derivatives, chloramphenicol, caffeine, prostaglandin, thymol , Camphor, squalene, plant and animal extracts or other products such as evening primrose oil, borage oil or carob oil, fish oil, cod liver oil, ceramide and ceramide-like compounds, perfume extract, green tea extract, Water lily extracts, licorice extracts, and witch hazel, antidandruff active compounds (e.g., selenium disulfide, zinc pyrithione, piroctone, olamine, clambazole, octopirox, polidocanol, and combinations thereof), and active compound complexes such as γ -Oryzanol and calcium pantothenate Active compounds complexes with calcium salts such as calcium, calcium chloride, and calcium acetate, NO synthase inhibitors such as nitroarginine; plants or plants containing catechol and bile acid esters of catechol, catechol or bile acid esters of catechol An extract derived from a part of the plant; polyphenols; flavones and derivatives thereof, sericoside, pyridoxol, vitamin K, biotin, and fragrances; α-hydroxy acids such as lactic acid or salicylic acid or their salts; Item 5. The cosmetic composition according to Item 4, wherein the cosmetic composition is selected from the group consisting of sodium lactate, calcium lactate, or lactate TEA, urea, allantoin, serine, sorbitol, milk protein, and panthenol.
Item 6
The active agent is selected from the group consisting of UV filters, anti-acne active agents, anti-aging active agents, anti-inflammatory agents, hair conditioning agents, antiperspirants or deodorants, whitening agents, self-tanning agents, and vitamins Item 5. The cosmetic composition according to Item 4, wherein
Item 7
A cosmetic composition comprising capryloylalanine ethyl ester and at least one UV filter.
Item 8
A cosmetic composition comprising capryloylalanine ethyl ester and at least one self-tanning agent or at least one whitening agent.
Item 9
A cosmetic composition comprising capryloylalanine ethyl ester and at least one antiperspirant and / or deodorant.
Item 10
A cosmetic composition comprising capryloylalanine ethyl ester and at least one anti-acne active agent and / or at least one anti-inflammatory active agent.
Item 11
A cosmetic composition comprising capryloylalanine ethyl ester and at least one anti-aging active.
Item 12
A cosmetic composition comprising capryloylalanine ethyl ester and vitamins.
Item 13
A cosmetic composition comprising capryloylalanine ethyl ester and at least one hair conditioning active.
Item 14
Use of capryloylalanine ethyl ester as a penetration enhancer for pharmacologically active substances and cosmetic active substances.
Item 15
A method for promoting skin penetration of a pharmacologically active substance and a cosmetically active substance by locally applying a composition comprising capryloylalanine ethyl ester.

Claims (10)

Capryoyl alanine ethyl ester , as well as UV filters, anti-acne active agents, anti-aging active agents, anti-inflammatory agents, hair conditioners, agents that have an effect on hair or hair follicles, antiperspirants or deodorants, whitening agents, self Tanning agent, peptide, oligopeptide, protein, acetylsalicylic acid, atropine, azulene, hydrocortisone, hydrocortisone 17-valerate, vitamins, vitamin B and vitamin D, vitamin B1, vitamin B12, vitamin D, vitamin A, reti Nylpalmitate, vitamin E, tocopheryl acetate, vitamin C, ascorbyl glucoside, niacinamide, panthenol, bisabolol polidocanol, unsaturated fatty acid, vitamin F, γ-linolenic acid, oleic acid, eicosapentaenoic acid, docosahexaenoic acid, chloramphenic acid Call, cafe , Prostaglandin, thymol, camphor, squalene, plant and animal extracts, evening primrose oil, borage oil or carob oil, fish oil, cod liver oil, ceramide, fragrance extract, green tea extract, water lily extract, licorice Extracts and witch hazel, antidandruff active compound, selenium disulfide, zinc pyrithione, piroctone, olamine, clambazole, octopirox, polidocanol, γ-oryzanol, calcium salt, calcium pantothenate, calcium chloride, calcium acetate, NO synthase inhibitor , Nitroarginine, catechol, bile acid esters of catechol, extracts derived from plants or parts of plants containing catechol or bile acid esters of catechol, leaves of camellia plants, polyphenols, flavones, sericosides, pyridoxides Sole, vitamin K, biotin, and aromatic substances, α-hydroxy acid, lactic acid or salicylic acid or salts thereof, sodium lactate, lactate Ca, lactate TEA, urea, allantoin, serine, sorbitol, milk protein, and panthenol At least one active agent including being more selective, the cosmetic composition.   2. Cosmetic composition according to claim 1, characterized in that it contains 0.1-90% by weight of capryloylalanine ethyl ester relative to the total composition.   3. The cosmetic composition according to claim 1, wherein the cosmetic composition is an emulsion composition.   A cosmetic composition comprising capryloylalanine ethyl ester and at least one UV filter.   A cosmetic composition comprising capryloylalanine ethyl ester and at least one self-tanning agent or at least one whitening agent.   A cosmetic composition comprising capryloylalanine ethyl ester and at least one antiperspirant and / or deodorant.   A cosmetic composition comprising capryloylalanine ethyl ester and at least one anti-acne active agent and / or at least one anti-inflammatory active agent.   A cosmetic composition comprising capryloylalanine ethyl ester and at least one anti-aging active.   A cosmetic composition comprising capryloylalanine ethyl ester and vitamins. Capryloylalanine ethyl ester , and
A hair growth stimulant that induces the growth of new hair cycles, increases the growth rate or increases the hair shaft diameter,
An agent having an effect on the hair which increases the amount of hair, the gloss of the hair, and the strength and thickness of the hair,
A drug having an effect on hair follicles, and
At least one hair regulatory agent is selected from the group consisting of hair growth inhibitors containing <br/>, cosmetic compositions.